Eric Van Cutsem, 1 Cathy Eng, 2 Josep Tabernero, 3 Elzbieta Nowara, 4 Anna Świeboda-Sadlej, 5

1. A Randomized, Phase 1/2 Trial of AMG 102 orAMG 479 in Combination With Panitumumab vs Panitumumab Alone in Patients With Wild‑Type KRAS Metastatic Colorectal Cancer (mCRC): Safety and Efficacy Results  Eric Van Cutsem,1 Cathy Eng,2 Josep Tabernero,3 Elzbieta Nowara,4 Anna Świeboda-Sadlej,5 Niall C. Tebbutt,6 Edith P. Mitchell,7 Irina Davidenko,8 Lisa Chen,9 Dominic Smethurst10 1University Hospital Gasthuisberg, Leuven, Belgium; 2The University of Texas M.D. Anderson Cancer Center, Houston, TX; 3Vall d'Hebron University Hospital, Barcelona, Spain; 4Instytut im. M. Sklodowskiej-Curie, Gliwice, Poland; 5Warszawski Uniwersytet Medyczny, Warszawa, Poland; 6Austin Health, Heidelberg, VIC, Australia; 7Thomas Jefferson University, Philadelphia, PA; 8Krasnodar City Oncology Center, Krasnodar, Russia; 9Amgen Inc., Thousand Oaks, CA; 10Amgen Ltd., Uxbridge, UK

2. Disclosures • Eric Van Cutsem: research funding from Amgen, Merck-Serono, Novartis, Pfizer, Roche, Sanofi-Aventis

3. Introduction • Panitumumab, a fully human monoclonal antibody against epidermal growth factor receptor (EGFR), has demonstrated efficacy in patients with wild-type KRAS mCRC in clinical trials1-4 • Rilotumumab (AMG 102) and ganitumab (AMG 479) are investigational, fully human monoclonal antibodies against hepatocyte growth factor (HGF; ligand for c-Met receptor) and insulin‑like growth factor 1 receptor (IGF-1R), respectively • Preclinical studies indicate that there is complex interdependence between the HGF/c-Met and IGF-1R and EGFR pathways5-10 • Combinations of agents that block these receptors are being investigated for their potential to generate additive/synergistic anticancer effects 6. Hynes NE, et al. Nat Rev Cancer. 2005;5:341-354. 7. Jo M, et al. J Biol Chem. 2000;275:8806-8811. 8. Ahmad T, et al. J Biol Chem. 2004;279:1713-1719. 9. Roudabush FL, et al. J Biol Chem. 2000;275:22583-22589. 10. Swantek JL, et al. Endocrinology. 1999;140:3163-3169. 1. Van Cutsem E, et al. J ClinOncol. 2007;25:1658-1664. 2. Amado RG, et al. J ClinOncol. 2008;26:1626-1634. 3. Peeters M, et al. J ClinOncol. 2010;28:4706-4713. 4. Douillard JY, et al. J ClinOncol. 2010;28:4697-4705. 5. Lesko E, et al. Front Biosci. 2008;13:1271-1280.

4. Rilotumumab and GanitumabMechanisms of Action Rilotumumab ( ) Rilotumumab (AMG 102) targets HGF, inhibiting downstream c-Met signaling Ganitumab (AMG 479) targets IGF-1R, inhibiting downstream signaling through PI3K/AKT and MAPK pathways

5. Study Schema • Amgen Trial 20060447; ClinicalTrials.gov identifier NCT00788957 Part 1 (Phase 1b)a Part 2 (Phase 2)b Part 3 (Phase 2)c Panitumumab+ Rilotumumab(AMG 102) Q2W R A N D O M I Z E R A N D O M I Z E Rilotumumab(AMG 102) Q2W Panitumumab+ Rilotumumab (AMG 102) Q2W Panitumumab+ Ganitumab(AMG 479) Q2W Ganitumab(AMG 479) Q2W Panitumumab+ Placebo Q2Wd aPanitumumab 6 mg/kg Q2W; rilotumumab (AMG 102) 10 mg/kg Q2W with dose de-escalation to 5 mg/kg as necessary; primary endpoint was incidence of dose-limiting toxicities bPanitumumab 6 mg/kg Q2W; rilotumumab (AMG 102) dose based on phase 1b; ganitumab (AMG 479) 12 mg/kg Q2W; primary endpoint was ORR cRilotumumab 10 mg/kg Q2W; ganitumab (AMG 479) 12 mg/kg Q2W; primary endpoint was ORR dPatients in the placebo arm of Part 2 with progressive disease or intolerance to treatment were eligible to participate in Part 3 DLT, dose-limiting toxicity; ORR, objective response rate; Q2W, every 2 weeks • Tumor assessments were performed by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) v1.0

6. Study Objectives Primary Objectives (Part 1 and Part 2) • Part 1: To identify a tolerable dose of rilotumumab (AMG 102) in combination with panitumumab based on the incidence and nature of dose-limiting toxicities (DLTs) • Part 2: To evaluate the efficacy as measured by the objective response rate (ORR) of rilotumumab (AMG 102) + panitumumab and ganitumab (AMG 479) + panitumumab vspanitumumab + placebo Other Key Objectives (Part 2) • Efficacy including progression-free survival (PFS) and overall survival (OS) • Safety • Pharmacokinetic analysis • Biomarker analysis

7. Key Eligibility Criteria • Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 • Histologically or cytologically confirmed wild-type KRAS mCRC by local or central testing • Progression during or following prior treatment with irinotecan- and/or oxaliplatin-based chemotherapy for mCRC • Glycosylated hemoglobin ≤ 8% • No prior treatment with EGFR, c-Met, or IGF-1R inhibitors

8. Statistical Considerations for Part 2 • Randomization was stratified by prior therapy (oxaliplatin or irinotecan vs both) • Bayesian analysis of response • This method compares the posterior distribution of the ORR for the experimental arms to that of the control arm to determine an Odds Ratio • An ORR prior distribution for panitumumabmonotherapy was derived from 4 previous trials (patients had received both prior oxaliplatin and irinotecan) • The ORR prior distributions for the combination arms were assumed to have the same mean as the panitumumab alone arm • The ORR posterior distribution for each arm combines the prior distributions with observed ORRs from the study • It was prespecified that if there was ≥ 90% probability that combination therapy was better than panitumumab alone as evaluated by objective tumor response, the combination was considered promising • If there was between 50% and 90% probability, the combination was considered indeterminate • If there was < 50% probability, the combination was considered not promising

9. Results Part 1 Results (Phase 1b) • In Part 1, no DLTs were reported for the first 6 DLT-evaluable patients receiving panitumumab in combination with rilotumumab (AMG 102) 10 mg/kg Q2W • The 10 mg/kg Q2W dose of rilotumumab (AMG 102) was used in Part 2 Part 2 Results (Phase 2) • 142 patients enrolled from 37 sites in 11 countries • The enrollment period was June 9, 2009 throughFebruary 5, 2010 • The date for data cut-off for this analysis was July 23, 2010 • Median follow-up is 6.9 months; follow-up is ongoing

10. Part 2: Patient Demographics and Disease Characteristics at Baseline aOne patient with ECOG performance score of 2 was enrolled in error; data from this patient were included in all efficacy and safety analyses bTwo patients had not received first-line therapy for mCRC; both patients had received oxaliplatin-based chemotherapy for non-metastatic CRC in the adjuvant setting and progressed on therapy before entering the study

11. Part 2: Primary EndpointOverall Response Rate aDisease control rate = CR + PR + SD bOR is calculated based on ORR; an OR > 1 favors the combination arm over panitumumab alone NE, not estimable • Responses were required to be confirmed at least 4 weeks after response criteria were first met

12. Part 2: Progression-Free Survival Panitumumab ± Rilotumumab (AMG 102) (AMG 102) (AMG 102) Panitumumab ± Ganitumab (AMG 479) (AMG 479) (AMG 479)

13. Adverse Events in Part 2(Any Grade in ≥ 20% or Grade 3/4 in ≥ 2 Patients) AE, adverse event • There were 9 grade 5 AEs; 1 occurred in the panitumumab alone arm and 4 occurred each in the combination arms • All except 1 were due to disease progression; 1 fatal AE was due to staphylococcal sepsis (panitumumab + ganitumab [AMG 479] arm) • None were reported to be related to investigational product

14. Conclusions • This is the first study to show promising evidence of efficacy by an HGF (c-Met pathway) inhibitor (rilotumumab [AMG 102]) when combined with panitumumab in patients with mCRC • The activity as assessed by ORR for patients receiving rilotumumab (AMG 102) plus panitumumab is promising (per prospectively specified Bayesian criterion) • Efficacy of ganitumab (AMG 479) plus panitumumab combination therapy as determined by ORR was indeterminate • The safety profiles of the drug combinations were generally similar to that of panitumumab alone with some exceptions, including a higher rate of grade 3/4 rash with rilotumumab and of hypomagnesemia with ganitumab • Analyses of biomarkers of response in serum and tissue samples are underway